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Vol. 40. Issue 5.
Pages 209-217 (May 2004)
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Vol. 40. Issue 5.
Pages 209-217 (May 2004)
Original Articles
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Analysis of Respiratory Muscle Structure and Tumor Necrosis and Insulin-Like Growth Factor Expression in Chronic Obstructive Pulmonary Disease: Are Samples Valid if Obtained During Thoracotomy Performed Because of Localized Pulmonary Neoplasia?
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C. Casadevalla, C. Coronella, J. Minguellab,c, L. Blancoa,d, M. Orozco-Levia,d, E. Barreiroa, J. Broquetasc,d, J. Geaa,d,e,
Corresponding author
jgea@imim.es

Correspondence: Dr. J. Gea. Servei de Pneumologia. IMIM-Hospital del Mar. Pg. Marítim, 27. 08003 Barcelona. España
a Unitat de Recerca en Múscul (URMA), IMIM-Hospital del Mar, Barcelona, Spain
b Secció de Cirurgia Toràcica, IMIM-Hospital del Mar, Barcelona, Spain
c Universitat Autònoma de Barcelona, Barcelona, Spain
d Servei de Pneumologia, IMIM-Hospital del Mar, Barcelona, Spain
e Universitat Pompeu Fabra, Barcelona, Spain
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Objective

Various methods have been used to obtain samples to study the structure of human respiratory muscles and the expression of diverse substances in them. Samples are most often obtained from autopsies, from muscle biopsies during thoracotomy performed because of a localized pulmonary lesion (TLL), and from ambulatory thoracoscopic biopsy in patients free of comorbidity (AT). The dis-advantage of the first 2 of these methods lies in the possibility of interference from factors related to the patient's death in the first case or from the disease that necessitated surgery in the second. Although AT is free from the disadvantages of the other 2 methods, it is impossible to obtain samples of the diaphragm—the principal respiratory muscle—with this procedure. The objective of this study was to analyze the fibrous structure of the external intercostal muscle of patients with chronic obstructive pulmonary disease and to quantify the expression of the principal inflammatory cytokine—tumor necrosis factor alpha (TNF-α)—and of insulin-like growth factor (IGF-1) in the same muscle, comparing the results obtained with TLL and AT samples.

Methods

Prospective and consecutive samples were taken of the external intercostal muscle (fifth space, anterior axillary line) in 15 patients with chronic obstructive pulmonary disease (mean [SD] age 66 [6] years; forced expiratory volume in 1 second 49% [9%] of predicted; PaO2 75 [9] mm Hg). Samples were taken during TLL (8 patients, all with pulmonary neoplasms but carefully selected in order to rule out systemic effects) or TA (7 patients). Patients with serious comorbidity were excluded from the second group. Samples were processed for structural analysis of fibers (immunohistochemical and enzymatic histochemical) and genetic expression of TNF-α and IGF-1 (real-time polymerase chain reaction).

Results

NO differences in the structure of fibers were found between the 2 groups. No differences were observed in the expression of TNF-α or IGF-1.

Conclusions

Using rigorous criteria, the TLL method appears to be suitable for studying the structural characteristics and expression of inflammatory cytokines and growth factors in the external intercostal muscle. Moreover, it can also be inferred that TLL is probably also useful for obtaining samples of the diaphragm, a muscle which cannot currently be sampled by any alternative method.

Key words:
Respiratory muscles
Fibers
TNF-α
Growth factor
Thoracotomy
Objetivo

LOS estudios estructurales y de expresión de diversas sustancias en músculos respiratorios de seres humanos se han servido de diversos modelos para la obtención de las muestras. Entre ellos destacan la toma de tejidos en autopsias, la biopsia muscular en el curso de una toracotomía por lesión pulmonar localizada (TLL) y la biopsia ambulatoria en sujetos sin comorbilidad (TA). Los 2 primeros modelos adolecen de las posibles interferencias de factores relacionados, respectivamente, con la muerte o la enfermedad que motiva el acto quirúrgico. La TA, aunque obvia los inconvenientes de los otros 2 modelos, no permite obtener muestras del diafragma, principal músculo respiratorio. El objetivo de este trabajo fue analizar la estructura fibrilar y expresión de la principal citocina inflamatoria -factor de necrosis tumoral alfa (TNF-α)- y del factor de crecimiento muscular insulina-like (IGF-1) en el músculo intercostal ex-terno de pacientes con enfermedad pulmonar obstructiva crónica, comparando los resultados obtenidos con los mode-los de TLL y TA.

Métodos

Se tomaron prospectiva y consecutivamente muestras del músculo intercostal externo (quinto espacio, línea axilar anterior) en 15 pacientes con enfermedad pulmonar obstructiva crónica (66 ± 6 años; volumen espiratorio forzado en el primer segundo del 49 ± 9% ref., presión arterial de oxígeno de 75 ± 9 mmHg). Las muestras se tomaron mediante TLL (8 pacientes, todos ellos con neoplasia pulmonar pero cuidadosamente seleccionados para descartar efec-tos sistémicos) o TA (7 pacientes), excluyéndose en el segundo caso la presencia de comorbilidad importante. Las muestras se procesaron para análisis estructural fibrilar (in-munohistoquímica e histoquímica enzimática) y de expresión génica de TNF-α e IGF-1 (reacción en cadena de la polimerasa en tiempo real).

Resultados

El análisis estructural de las fibras no mostró diferencias entre ambos grupos. Tampoco se observaron diferencias en la expresión de TNF-α o IGF-1.

Conclusions

Con criterios de selección rigurosos, el modelo de TLL parece adecuado para el estudio de las caracte-rísticas estructurales y de expresión de citocinas inflamato-rias y factores de crecimiento en el músculo intercostal externo. Puede además inferirse que probablemente la TLL también sea útil para esos objetivos en el caso del diafragma, para el que no existe una técnica alternativa en la actualidad.

Palabras clave:
Músculos respiratorios
Fibras
TNF-α
Factor de crecimiento
Toracotomía
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Dr. C. Coronell's work was financed by a research grant from the Spanish Ministry of Science and Technology (Beca de Movilización de Investigadores y Profesores Extranjeros del Ministerio de Ciencia y Tecnología ref. 72129052)

This study was jointly financed by the European Union's V Framework Program (ref. QLRT-2000-00417), the Spanish Ministry of Science and Technology's National Research and Development Plan (Plan Nacional I + D del Ministerio de Ciencia y Tecnología ref. SAF 2001-0426), and by the Red RESPIRA (RTIC C03/11, FIS, ISC III) of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR).

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